Carnosine and Diabetic Nephropathy

Peters, Verena; Yard, Benito A.; Schmitt, Claus Peter

doi:10.2174/0929867326666190326111851

Cited by 32 publications

(22 citation statements)

References 94 publications

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“…Several studies could demonstrate that carnosine and anserine have specific dipeptide functions such as antioxidant activity [14,28] which cannot be explained by their corresponding amino acids alone. For example, treatment with carnosine or anserine prevented alterations of renal function in diabetic (db/db) mice [29][30][31]. Additionally, for proline-containing dipeptides the biological activities seem to be not only based on the free amino acid alone [1]; for Tyr-containing dipeptides [32] an inhibitory effect on ACE activity has been demonstrated, and Tyr-Asp improves plant tolerance to oxidative stress by directly interfering with glucose metabolism [33].…”

Section: Discussionmentioning

confidence: 99%

A Novel UPLC-MS/MS Method Identifies Organ-Specific Dipeptide Profiles

Heidenreich

Pfeffer

Kracke

et al. 2021

IJMS

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Background: Amino acids have a central role in cell metabolism, and intracellular changes contribute to the pathogenesis of various diseases, while the role and specific organ distribution of dipeptides is largely unknown. Method: We established a sensitive, rapid and reliable UPLC-MS/MS method for quantification of 36 dipeptides. Dipeptide patterns were analyzed in brown and white adipose tissues, brain, eye, heart, kidney, liver, lung, muscle, sciatic nerve, pancreas, spleen and thymus, serum and urine of C57BL/6N wildtype mice and related to the corresponding amino acid profiles. Results: A total of 30 out of the 36 investigated dipeptides were detected with organ-specific distribution patterns. Carnosine and anserine were most abundant in all organs, with the highest concentrations in muscles. In liver, Asp-Gln and Ala-Gln concentrations were high, in the spleen and thymus, Glu-Ser and Gly-Asp. In serum, dipeptide concentrations were several magnitudes lower than in organ tissues. In all organs, dipeptides with C-terminal proline (Gly-Pro and Leu-Pro) were present at higher concentrations than dipeptides with N-terminal proline (Pro-Gly and Pro-Leu). Organ-specific amino acid profiles were related to the dipeptide profile with several amino acid concentrations being related to the isomeric form of the dipeptides. Aspartate, histidine, proline and serine tissue concentrations correlated with dipeptide concentrations, when the amino acids were present at the C- but not at the N-terminus. Conclusion: Our multi-dipeptide quantification approach demonstrates organ-specific dipeptide distribution. This method allows us to understand more about the dipeptide metabolism in disease or in healthy state.

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Section: Discussionmentioning

confidence: 99%

A Novel UPLC-MS/MS Method Identifies Organ-Specific Dipeptide Profiles

Heidenreich

Pfeffer

Kracke

et al. 2021

IJMS

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“…Carnosine scavenges carbonyls [ 6 , 7 ], inhibits glycation [ 8 ], prevents AGE formation and has antioxidant actions. Supplementation of carnosine in diabetic rodents increases renal carnosine concentrations [ 32 ] and consistently preserves renal morphology and function [ 20 ]. In humans carnosinemia, due to CN1 deficiency may be a non-disease; whereas accumulation of carnosine should protect against long-term sequelae of reactive metabolites accumulating, e.g., in diabetes and chronic renal failure [ 3 , 20 ] and may prevent cancer development [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

“…Supplementation of carnosine in diabetic rodents increases renal carnosine concentrations [ 32 ] and consistently preserves renal morphology and function [ 20 ]. In humans carnosinemia, due to CN1 deficiency may be a non-disease; whereas accumulation of carnosine should protect against long-term sequelae of reactive metabolites accumulating, e.g., in diabetes and chronic renal failure [ 3 , 20 ] and may prevent cancer development [ 33 ]. Efficacy of therapeutic carnosine supplementation in humans, however, is limited by a highly active serum CN1 largely preventing major increases in serum carnosine concentrations [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

“…In kidneys of mice and men, anserine and carnosine are present at high concentrations, with anserine concentrations exceeding those of carnosine [ 19 ]. Supplementation of carnosine in diabetic rodents consistently improved renal histology and function [ 20 ], vascular permeability [ 21 ], and wound healing [ 22 ], but also glucose homeostasis [ 23 , 24 , 25 , 26 ]. Whether the beneficial effects of carnosine resulted from interference with reactive metabolite-induced molecular pathomechanisms or primarily via improving glucose homeostasis is yet unclear.…”

Section: Introductionmentioning

confidence: 99%

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A Global Cndp1-Knock-Out Selectively Increases Renal Carnosine and Anserine Concentrations in an Age- and Gender-Specific Manner in Mice

Weigand

Colbatzky

Pfeffer

et al. 2020

IJMS

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Carnosinase 1 (CN1) is encoded by the Cndp1 gene and degrades carnosine and anserine, two natural histidine-containing dipeptides. In vitro and in vivo studies suggest carnosine- and anserine-mediated protection against long-term sequelae of reactive metabolites accumulating, e.g., in diabetes mellitus. We have characterized the metabolic impact of CN1 in 11- and 55-week-old Cndp1-knockout (Cndp1-KO) mice and litter-matched wildtypes (WT). In Cndp1-KO mice, renal carnosine and anserine concentrations were gender-specifically increased 2- to 9-fold, respectively in the kidney and both most abundant in the renal cortex, but remained unchanged in all other organs and in serum. Renal oxidized/reduced glutathione concentrations, renal morphology and function were unaltered. In Cndp1-KO mice at week 11, renal asparagine, serine and glutamine levels and at week 55, renal arginine concentration were reduced. Renal heat-shock-protein 70 (Hspa1a/b) mRNA declined with age in WT but not in Cndp1-KO mice, transcription factor heat-shock-factor 1 was higher in 55-week-old KO mice. Fasting blood glucose concentrations decreased with age in WT mice, but were unchanged in Cndp1-KO mice. Blood glucose response to intraperitoneal insulin was gender- but not genotype-dependent, the response to intraperitoneal glucose injection was similar in all groups. A global Cndp1-KO selectively, age- and gender-specifically, increases renal carnosine and anserine concentrations, alters renal amino acid- and HSP70 profile and modifies systemic glucose homeostasis. Increase of the natural occurring carnosine and anserine levels in the kidney by modulation of CN1 represents a promising therapeutic approach to mitigate or prevent chronic kidney diseases such as diabetic nephropathy.

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“…Elbarbary NS et al reported that carnosine could reduce urine alpha-1 microglobulin, which is a urine biomarker of glomerular and tubular injury among diabetic patients, as well as urinary TGF-β [12]. Several studies in animal models also demonstrated antiin ammatory, anti-oxidant, antiglycation, antiproteinuric and vasculoprotective effects of carnosine [13,14].…”

Section: Discussionmentioning

confidence: 99%

Effect of Oral Carnosine Supplementation on Urinary TGF-β in Diabetic Nephropathy: a Randomized Controlled Trial

Siriwattanasit

Satirapoj

Supasyndh

2020

Preprint

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Background: Activation of the transforming growth factor beta (TGF-b) pathway is a significant contributor to the pathogenesis of diabetic nephropathy. Carnosine is an amino acid that can inhibit TGF-b synthesis. We tested the hypothesis that carnosine supplement added to standard therapy will result in reduced urinary TGF-b levels among patients with diabetic nephropathy. Methods: We randomly assigned 40 patients with diabetic nephropathy and albuminuria 30-299 mg/day to treatment with carnosine (2 g/day) or placebo for 12 weeks. Urinary TGF-b level was determined using ELISA, urine albumin was ascertained by immunonephelometric assay, and renal function and metabolic profiles were determined at baseline and during 12 weeks of active treatment. Primary outcome was decrease in urinary levels of TGF-b.Results: The 2 groups were comparable for baseline characteristics, blood pressure, urine albumin, urine TGF-b and renal function measurements. Urinary TGF-b significantly decreased with carnosine supplement (-17.8% of the baseline values), whereas it tended to increase with placebo (+16.9% of the baseline values) (between-group difference P <0.05). However, blood urea nitrogen, serum creatinine, glomerular filtration rate and other biochemical parameters remained unchanged during the study period including urinary albuminuria. Both groups were well tolerated with no serious side-effects.Conclusions: These data indicated an additional renoprotective effect of oral supplementation with carnosine to decrease urinary TGF-b level that serves as a marker of renal injury in diabetic nephropathy. Trial registration Thai Clinical Trials, TCTR20200724002. Retrospectively Registered 24 July 2020.

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Carnosine and Diabetic Nephropathy

Cited by 32 publications

References 94 publications

A Novel UPLC-MS/MS Method Identifies Organ-Specific Dipeptide Profiles

A Novel UPLC-MS/MS Method Identifies Organ-Specific Dipeptide Profiles

A Global Cndp1-Knock-Out Selectively Increases Renal Carnosine and Anserine Concentrations in an Age- and Gender-Specific Manner in Mice

Effect of Oral Carnosine Supplementation on Urinary TGF-β in Diabetic Nephropathy: a Randomized Controlled Trial

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